Representative among main diseases of people these days is cancer. Studies on cancer are actively ongoing, particularly in the areas of high-prevalence cancers including lung cancer, liver cancer, stomach cancer, etc., but there are fewer studies being conducted on low-prevalence cancers including esophageal cancer, colorectal cancer, pancreatic cancer, etc.
In particular, pancreatic cancer usually does not cause recognizable symptoms in its early stages, and the disease is typically not diagnosed due to its minor symptoms such as pain, weight loss, etc., until it has spread beyond the pancreas itself to the whole body. Moreover, pancreatic cancer is generally poor in survival rate, and thus periodical diagnosis is very important. Clinical symptoms of pancreatic cancer are, in most part, slowly exposed, and patients with pancreatic cancer most commonly suffer from feebleness, anorexia, and weight loss. Found to have a five-year survival rate of 1-4% with a median survival time of 5 months, pancreatic cancer is very fatal and is the poorest in prognosis among human cancers. After diagnosis, it is found that 80-90% of people are impossible to treat by hopeful curative resection. This is one of the main reasons for the generally highly poor prognosis. Pancreatic cancer is predominantly treated with chemotherapy. Therefore, in comparison to other cancers, there is a desperate need for an early diagnosis method of pancreatic cancer.
Although known so far to be useful in treating pancreatic cancer, several anticancer agents including 5-fluorouracil, gemcitabine, and tarceva, exhibit very low curative effects and a reaction rate of only around 15% for cancer treatment. These situations suggest there is a pressing request for more effective early diagnosis and therapy for pancreatic cancer whereby the prognosis can be improved. In this context, appropriate diagnosis and therapy for a precursor lesion of pancreatic cancer, that is, a pre-stage of pancreatic cancer, is very important for the therapeutic result.
Diagnosis of pancreatic cancer or a precursor lesion thereof is determined upon hematologic examination (CA19-9), gastrointestinography and duodenography with X-ray contrast media, cholangiography through the skin and the liver, or endoscopic retrograde cholangiopancreatograhy. Many disease lesions can be detected by such methods, but currently, ultrasonography and computed tomography are the most preferred. More deliberate biopsy methods might result in relatively more accurate outcomes. The diagnosis methods described above are used because they are generally accurate; however, subjects are unwilling to undergo examination because such diagnosis methods are uncomfortable or painful. Hence, there is need for method of diagnosing pancreatic cancer or a precursor lesion thereof conveniently and rapidly.
Recently, extensive medical examination using imaging diagnosis technologies including abdominal ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and the like have been able to frequently discover malignant lesions at or around the pancreas, even though they tended to detect lesions in organs other than the pancreas. Lesions that appear as cysts as measured by imaging diagnosis are clinically important because they may cover various diseases from benign to premalignant and malignant lesions in terms of pathologic traits.
In spite of much advance in imaging diagnosis such as in CT, MRI, etc., it is still difficult to accurately discriminate cystic lesions of the pancreas having various pathologic traits from benign to premalignant and malignant lesions, prior to surgery. Hence, it is clinically important to determine whether a cystic lesion in the pancreas is a tumor lesion that is prone to malignant alteration, and whether it, if having potential for malignant alteration, remains premalignant or has already undergone malignancy.
Korean Patent No. 10-0819122 and Korean Patent Unexamined Application Publication No. 2012-0082372 disclose technologies using various pancreas cancer markers including matrilin, transthyretin, and stratifin. In addition, Korean Patent Unexamined Application Publication No. 2009-0003308 describes diagnosis of pancreatic cancer through the detection of an expression level of REG4 in a blood sample from a subject. Korean Patent Unexamined Application Publication No. 2012-0009781 describes an analysis method for measuring an XIST RNA expression level in a cancer tissue from a subject, whereby information on the onset of pancreatic cancer in the subject can be provided. Korean Patent Unexamined Application Publication No. 2007-0119250 discloses a family of new LBFL313 genes that are expressed in different patterns between normal pancreatic tissues and pancreatic cancer tissues. U. S. Patent Application No. 2011/0294136A1 discloses a diagnosis method of pancreatic cancer using biomarkers including keratin 8 protein. However, diagnostic efficiency and accuracy greatly differ from one marker to another. Therefore, there is a pressing need for an excellently efficient marker and a diagnosis method using the same.